p16 expression in patients with cervical cancer and its prognostic significance: meta-analysis of published literature

Eur J Obstet Gynecol Reprod Biol. 2014 Dec:183:64-9. doi: 10.1016/j.ejogrb.2014.10.016. Epub 2014 Oct 24.


Objectives: p16, a tumour suppressor, is unable to express its suppressive effects following interaction with E7-retinoblastoma protein. Previous reports have suggested that p16 immunostaining allows precise identification of cervical intra-epithelial neoplasia and cervical cancer lesions in biopsies. The prognostic value of p16 expression in cervical cancers has been evaluated for several years, but the results remain controversial. As such, the authors undertook a systematic review and meta-analysis of studies assessing the impact of p16 expression on overall survival and disease-free survival.

Study design: Medline, Embase and China National Knowledge Infrastructures were searched to identify studies on the prognostic impact of p16 expression in patients with cervical cancer. In total, 1070 patients from 10 eligible studies were included in the analysis. Pooled risk ratios (RRs) with 95% confidence intervals (95% CI) were calculated.

Results: A significant association was found between p16 expression and increased disease-free survival (RR 0.60; 95% CI 0.44-0.82; p=0.001). However, no significant association was found between p16 and overall survival.

Conclusion: p16 expression may be predictive of a favourable prognosis in patients with cervical cancer. However, large-scale, multicentre and well-matched cohort studies are warranted to confirm this finding.

Keywords: Immunohistochemistry; Meta-analysis; Survival; p16.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Biopsy
  • Cyclin-Dependent Kinase Inhibitor p16
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Neoplasm Staging
  • Predictive Value of Tests
  • Prognosis
  • Survival Rate
  • Uterine Cervical Dysplasia / metabolism*
  • Uterine Cervical Dysplasia / mortality*
  • Uterine Cervical Dysplasia / pathology
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / mortality*
  • Uterine Cervical Neoplasms / pathology


  • Biomarkers, Tumor
  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Neoplasm Proteins